The determination of the optical properties of tissues is of fundamental importance in many fields of medicine, both for diagnostic and monitoring purposes. It is well known that light of differing wavelengths penetrates differently in various tissues. In the near infrared region, for example, (about 650 nm to about 1000 nm), light of this wavelength penetrates several centimeters through tissue. It is intended that the term "light" includes visible light and other electromagnetic radiation as well which is invisible to the human eye, for example, infrared and ultraviolet.
Because of the capability of various forms of light to penetrate tissue for several centimeters, photometric or spectroscopic methods can be used to measure the concentration of tissue metabolites such as hemoglobin by the measuring of the absorption of the light at one or more wavelengths.
In the prior art, the absolute determination of the concentration of a substance can be obtained by the measurement of the light transmitted through a sample of known thickness. Such a transmission measurement enables one to determine the absorption coefficient. Using this, the concentration of the measured substance can be calculated using the molar extinction coefficient of that substance via the Beer-Lambert law.
In the event of interference caused by more than one substance being present, measurement at different wavelengths can provide a method to determine the concentration of one or more different chemical species present, assuming that the materials present have different absorption spectra. The success of this method depends on the precision of the measurement and on the number of different substances present.
Additional problems arise in the photometry of tissues and other materials having high turbidity, such as emulsions. For purposes of this disclosure, it is to be understood that the term "tissue" may include living materials, but can also include non-living materials such as emulsions when it is desired to obtain similar data from such emulsions as is done by this invention with tissues. A measurement of the light transmitted through a slab of tissue has in the prior art been not practical, using non-invasive methods, except for special, thin regions of the body where light can shine entirely through the tissue and be detected on the other side. An example of this is a clinically used photometric blood oxygen sensor, which fits on the finger tip and shines directly therethrough to give real time oxygen concentration data.
An exception to this is found in Gratton, et al. patent application Ser. No. 08/168,813, filed Dec. 16, 1993, cited above, in which a method and apparatus is provided for quantitative measurement of blood oxygen saturation by photometry of the arm, thigh, or the like.
In tissue photometry, the amount of transmitted light depends not only on the absorption of the medium being analyzed, but also on the scattering properties thereof. This light scattering greatly increases the complexity of photometric analysis of tissue, emulsions, and similar materials, since light scattering produces an unpredictable variation of the amount of light transmitted, which can vary significantly between various samples of tissues and the like.
Many different methods have been proposed to deal with this problem of scattering in photometric processes. For example, empirical corrections based on the type of tissue to be measured have been used to account for the effect of scattering on the absorption properties. For reflection measurements, theoretical models have been used to calculate the albedo of a surface. The success of all of these models has been poor, although there are commercially available instruments based upon those principles. A major problem is that in order to obtain a reasonable estimate of the concentration of a substance in tissue, some sort of a priori calibration must be performed, based on a statistical analysis of a large number of corresponding tissue samples. However, the range of variation of scattering within tissues from various individuals results in fundamentally unpredictable results, with the photometric results being strongly modified by factors such as skin color, and the amount of lipids in muscles.
The Hamamatsu Company of Japan in 1990 introduced a simple tissue spectrometer called NIRO 500 for the measurement of tissue oxygenation and total blood volume for neonatal monitoring. The principles of this device are as disclosed in Cope U.S. Pat. No. 5,032,024. The instrument is a steady state instrument, and is based on four different laser diodes emitting in the near infrared range. The light is brought to the tissue using a fiber optic system. The measurement is purely a steady-state one, with the optical path length in the tissue being not measurable. Thus, only relative quantities can be obtained, rather than absolute concentrations of materials being measured.
Some materials such as glucose lack a strong absorption line at a convenient wavelength of light which can be used for photometric determination through tissue. In this circumstance, the problem of photometrically determining concentrations of glucose or other metabolites in tissue or materials in an emulsion becomes quite difficult.
By this invention, a method is provided in which the concentration of an ingredient of a highly scattering medium, for example glucose in tissue, can be determined and monitored in real time on a relative concentration basis by a photometric technique in which no band of the light is strongly absorbed by the material being monitored.